Huby R D, Carlile G W, Ley S C
Division of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom.
J Biol Chem. 1995 Dec 22;270(51):30241-4. doi: 10.1074/jbc.270.51.30241.
Two molecules involved in signal transduction via the T cell antigen receptor, namely the protein-tyrosine kinase ZAP-70 and the proto-oncoprotein Vav, were found to be constitutively associated with tubulin in Jurkat T cells. Both were able to bind to tubulin independently of one another, as determined by transient transfection into COS-7 cells. The ZAP-70 associated with tubulin was preferentially tyrosine-phosphorylated after T cell antigen receptor stimulation of Jurkat T cells, suggesting that this interaction was functionally significant. Vav was also found to co-immunoprecipitate with ZAP-70 from cell extracts depleted of tubulin. This raised the possibility that Vav might be a substrate for ZAP-70 protein-tyrosine kinase activity. However, tyrosine phosphorylation of Vav preceded that of ZAP-70, indicating that Vav was unlikely to be a downstream target of ZAP-70. The association of ZAP-70 and Vav with tubulin implies that the microtubules may be involved in the signaling function of these two molecules, perhaps by targeting them to their appropriate intracellular location.
通过T细胞抗原受体参与信号转导的两个分子，即蛋白酪氨酸激酶ZAP-70和原癌蛋白Vav，被发现与Jurkat T细胞中的微管蛋白持续相关。通过瞬时转染到COS-7细胞中确定，二者均能够彼此独立地与微管蛋白结合。在Jurkat T细胞受到T细胞抗原受体刺激后，与微管蛋白相关的ZAP-70优先发生酪氨酸磷酸化，这表明这种相互作用具有功能意义。还发现Vav可与来自耗尽微管蛋白的细胞提取物中的ZAP-70进行共免疫沉淀。这增加了Vav可能是ZAP-70蛋白酪氨酸激酶活性底物的可能性。然而，Vav的酪氨酸磷酸化先于ZAP-70，这表明Vav不太可能是ZAP-70的下游靶点。ZAP-70和Vav与微管蛋白的关联意味着微管可能参与这两个分子的信号传导功能，也许是通过将它们靶向到适当的细胞内位置来实现。
